Antiseptic detergent compositions



of an alkylated halogenated United States Patent Cfiice Patented Mar. 12, 1963 3,081,266 ANTISEPTIC DETERGENT COMPOSITIONS Darwin R. Noel and Robert E. Casely, Chicago, 11]., assignors, by mesne assignments, to Armour and Company, Chicago, 111., a corporation of: Delaware No Drawing. Filed Sept. 27, 1955, Ser. No. 537,057 2 Claims. (Cl. 252-107) This invention relates to antiseptic compositions having synergic eiiect. in one of its aspects, this invention relates to improved germicidal cleansing compositions containing as their essential active germicidal ingredients a synergistic combination of an unalkylated halogenated bisphenol and an alkylated halogenated bisphenol in which the alkyl groups contain from 1 to 4 carbon atoms.

The popularity of germicidal cleansing compositions for laundry and toilet use has increased tremendously over the past few years. In fact, it has been estimated that 20% of the bar soap sales now are of products containing a germicidal agent, and this percentage is steadily increasing. currently in use but the halogenated bisphenols appear to be the most widely accepted because of their activity, compatability, and commercial availability. One of the desirable compounds of this class is 2,2-dihydroxy- 3,5,6,3',5',6-hexachlorodiphenyl methane, commonly known as hexachlorophene, which is now in widespread commercial use. The action of halogenated bisphenols such as hexachlorophene when incorporated in soap, the proportions required, and other pertinent information is set out more fully in U.S. Patent No. 2,635,077 to Kunz et *al.

There are certain inherent disadvantages to the use of halogenated bisphenols. For example, they are photosensitive and tend to cause discoloration in the finished product on exposure to ligh Also, they are somewhat toxic and present a potential hazard to domestic animals .which are prone to eat things,.even soap. Therefore, it

would be desirable to diminish these disadvantages without adversely afiecting the germicidal activity of the halo- 'genated bisphenol. Viewed in a different light, it would also be worth while if the disadvantages could be maintained at the present level and the germicidal activity of the halogenated bisphenol increased. We have discovered that these objects can be accomplished through the production of the synergic effect.

'In accordance with the present invention, the germicidal activity of unalkylated halogenated bisphenol is enhanced, synergized or potentiated by the incorporation therewith bisphenol in which the alkyl groupscont ain from 1 to 4 carbon atoms. The products of this invention, therefore, are antiseptic compositions containing as their essential active ingredient a synergistic combination of an unalkylated halogenated bisphenol and an alkylated halogenated bisphenol in which the alkyl groups contain from 1 to 4 carbon atoms.

. The unalkylated halogenated bisphenol used in accordance with the present invention can be represented by the following structural formula: i

' no on X11 7 I X11 wherein X represents a halogen such as chlorine or bromine, n represents an integer of from 1 i 3, and R There are a number of germicidal agentsrepresents a divalent alkylene radical having 1 to 4 carbon atoms such as z z z, 3)-, 3)2 CH =CH CH and the like. The preferred compounds are symmetrical in structural configuration.

Specific examples of the unalkylated halogenated bisphenols include 2,2'-dihydroxy halogenated diphenyl methanes such as 2,2-dihydroxy-3,5, 6,35','6'-hexachlorodiphenyl methane '(hexachlorophene), 2,2'-dihydroxy- 3,5,3',5 tetrachlorodiphenyl methane, 2,2 dihydroxy- 4,5,4','5' tetrachlorodiphenyl methane, 2,2 dihydro-Xy- 3,4,3,4-tetrachlorodiphenyl methane, and 2,2'-dihydroxy- 5;5-dibromodiphenyl methane.

The alkylated halogenated bisphenols used in conjunction with the unalkylated halogenated bisphenols in the present invention can be any suitable bisphenol composi tion characterized by the presence of short-chain alkyl groups in the aromatic rings. These substances can be {epresented according to their chemical structure as folows:

HO OH wherein X represents a halogen such as chlorine or bromine, n is an integer of from 1 to 3, R is an alkyl group containing from 1 to 4 carbon atoms and Y is a divalent radical including alkylene radicals having from 1 to 4' carbon atoms such as illustrated above, are used together in an antiseptic composition, a germicidal effect is achieved which is greater than the mere total of the individual effects of the individual ingredients. This has importance in cases where the activity of the unalkylated halogenated bisphenol is desired to be increased without employing higher concentrations, and in other cases it assumes an even greater importance from an economic standpoint, since the presence of the alkylated halogenated bisphenol enables a ubstantial reduction in the concentration of the germicidal agent while at the same time retaining the desired level of germicidal activity.

What the-actual mechanism of the potentiating or synergistic eiiect might be, we are unable to explain. The invention relates to the synergistic cooperation of these two types of compounds when used in minor proportions in an antiseptic composition, and especially an antiseptic detergent composition, and the discovery that this synergistic phenomenon occurs even at pH conditions existing in soap and detergent formulations provides one of the important phases of the present invention.

Relatively small amounts of the unalkylatcd halogenated bisphenol and the alkylated halogenated bisphenol are sufficient for the increased germicidal effect of the present invention. Satisfactory results are obtained when the combined weight of the two types of bisphenols are from 1 to 3% of the total weight of the composition. The objects of the invention are achieved when the weight ofthe unalkylated halogenated bisphenol is about 0.1% to 3% and the 'alkylated halogenated bisphenol is about 3% to 0.1% by Weight based upon the detergent or soap. The preferred weight is a concentration of about 0.25% to 1.75% of the unalkylated halogenated *bisphenol and about 1.75% to about 0.25% of the alkylated halogenated bisphenol, and an excellent product is one containing a detergent soap and about 1% of each of the unalkylated halogenated bisphenol and the alkylated halogenated bisphenol. It will be understood that even concentrations below the ranges just set out will provide some degree of germicidal eflYect and that substantially higher concentrations than those given will provide satisfactory results, although there are certain practical considerations, such as the cost of the bisphenol and a certain impairment in detergent properties, which limit the desirability of including greater amounts of the germicide in the soap.

The term soap refers to the water-soluble ammonium, metallic, organic base salts of various fatty acids, which are chiefly lauric, oleic, stearic, and palrnitic acids. As used in this specification and claims, the term is intended to cover all products in which soap is a major constituent, for example, bar, flake, powdered, soft and liquid soaps; shaving creams, toothpastes, cleansing creams, etc.

The invention also contemplates the use of anionictype synthetic detergents in place of the soap. The anionic-type synthetics suitable for use in the invention can be described as those detergents having pronounced cleansing power and including in their molecular structure an alkyl radical containing from 6 to 18 carbon atoms and a sulfonic acid or sulfuric acid ester radical. Either organic base, ammonium, sodium or potassium salts of the anionic-type detergents can be used. The main types of detergents falling within this category are the alkyl-aryl sulfonates, such as sodium or potassium dodecyl benzene sulfonate, sodium or potassium octadecyl benzene sul-fonate and sodium; or potassium octyl naphthalene sulfonate; the alkyl sulfates such as sodium or potassium salts of dodecyl, hexadecyl, and octadecyl sulfate; the sulfonated fatty acid amides such as the sodium or potassium salts of the oleic acids of methyl taurine; and the sulfonated monoglycerides such as the mono-coconut oil fatty acid ester of 1,2-hydroxy propane-3-sodium sulfonate.

The unalkylated halogenated bisphenol and the alkylated halogenated :bisphenol can be added to the soap or the detergent by any suitable method which results in a uniform'distr'ibution of the additives throughout the entire mass. A high satisfactory dispersion method of carrying out the addition step is described more fully in the copending application Serial No. 263,302, filed December 26, 1'95 1, now abandoned. V

Specific examples illustrating the invention are setout a's'follows:

EXAMPLE I The procedure employed for determining the minimum effective dose (M.E.D.) represents a variation of a method published in the Journal of General Microbiology, volume 10, No. 2, April 1954, on Observations on the Mode of Action of Antibiotic Synergism and Antagonism, Department of Microbiology, University of California School of Medicine. In place of the plate counts used in the published method, the end point of chemical activity in the present method was taken as that point at which no growth was apparent in the broth tubes.

The minimum effective dose of 2,2-dihydroxy-3,5,6,3', 5',6' -hexachlorodiphenyl methane (hexachlorophene), 2,2-dihydroxy-3,3'-dimethyl 5,5 dichlorodiphenyl sulfide, and 2,2-hydroxy 3,3 dimethyl 5,5 di-chlorodiphenyl trichloroethane were first determined by diluting the prepared stock solutions of the test chemicals in a series of tubes containing 10 ml. of nutrient broth culture medium. Each successive tube in the series contained the test chemicals at /2 the concentration of the previous tube. 0.1 ml. of a 1-10 dilution of a 24 hour broth culture of the test organisms M. pyogenes var. aureus was then added to each tube of the broth tubes in the series. The period of incubation for all tubes was 48 hours at a temperature of 37 C. The end point or minimum effective dose of chemical was taken as that point at which no growth was apparent in the highest dilution of the chemical in the broth tube.

After determining the minimum effective doses of the individual test chemicals, each of the other two test chemicals were combined with hexachlorophene in a series of broth tubes at a concentration in broth at sub-inhibitory and near sub-inhibitory levels of all chemicals. There were two series of 16 tubes each, each tube containing hexachlorophene and the individual test chemical in a different ratio. Inoculation with the test organism M. pyogenes var. aurells was made in each tube in the series by adding to each tube 0.1 ml. of a 1-10 dilution of a 24 hour broth culture of the organism. The incubation period was 48 hours at a temperature of 37 C. The determination of synergistic activity was made in the tube or tubes having the lowest sub-inhibitory concentration of both hexachlorophene and the individual test chemical showing no apparent growth of the test organism.

The results of these tests setting forth the minimum eiiective dose in micrograms per milliliter is set forth in Table I.

Table l M.E.D., Growth Combined Test Chemicals I y/ml. after Effect 48 hrs.

2,2-dihydroxy-3,5,6,3,5,6'-

hgzrachlorodiphenyl methane 1 0.2 0 2,2 dihydroxy-3,3-dimcthyl 5g; -dichlorodipheny1 sulfide 0.5 0 2,2-dihydroxy-3,3-dimethyl-5,5-

dichlorodiphenyl trichloroethane (C). 0.5 0 (A)+(B) 0 synergism. (AH-(C) 0 synergism.

Composition I A B I C I D J E Fine Art neutral white toilet soap 2,2 dlhydroxy 3,5,6,3,5,6' hexachlorodiphenyl methane" 2,2 dihydroxy 3,3 methyl-5,5 diehlorodiphenyl sulfide 2 1 2,2 dihydroxy 3,3 dimethyl 5,5 dichlorodiphenyl triehloroethane 2 1 Aliquots of each of the above described compositions containing 2% by weight active ingredient were added Table III Composition A i B 0 D E Period of Incubation 48 48 48 48 48 Amount 0! growth 3+ 3+ 3+ 1+ Legend:

- no growth (complete inhibition). 1+ very slight growth (l-100 colonies present) 2+ light to moderate growth (100-1000 colonies present) 3+ normal heavy growth (over 1000 colonies present) While this invention has been described and exemplified in terms of its preferred embodiments, those skilled in the art will appreciate that variations can be made without departing from the spirit and scope of the invention.

We claim:

1. An antiseptic detergent composition comprising a water-soluble soap and an antiseptic combination having a synergistic effect consisting of from about 0.1% to about 3.0% by weight-based upon the soap of 2,2-di- 6 hydroxy-3,S,6,3,5',6'-hexachlorodiphenyl methane and from about 3.0% to about 0.1% by weight based upon the soap of 2,2-dihydroxy-3,3-dimethyl-5,5'-dichlorodiphenyl sulfide.

2. An antiseptic detergent composition comprising water soluble soap and about 2% by weight based upon the soap of a mixture of equal parts by weight of 2,2- dihydroxy-3,5,-6,3',5,6-hexach1orodiphenyl methane and 2,2 dihydroxy 3,3-dimethyl 5,5 dichlorodiphenyl sulfide.

References Cited in the file of this patent UNITED STATES PATENTS 2,353,735 Kunz et al. July 18, 1944 2,535,077 Kunz et al. Dec. 26, 1950 2,623,907 Moyle Dec. 30, 1952 2,695,317 Cutler Nov. 23, 1954 2,814,597 Wenneis et a1. Nov. 26, 1957 OTHER REFERENCES U.S.D.A. publication, ET-223, June 1945, The Evidence Required to Show Synergistic Action of Insecticides and a Short Cut in Analysis, by Wadley, 7 pages.

Drug & Cosmetic Industry, November 1955, vol. 77, No. 5, page 714, article by Elder et al.

Antibiotics and Chemotherapy, January 1958, vol. 8, No. 1, pages 8-20, article by Garrett. 

1. AN ANTISEPTIC DETERGENT COMPOSITION COMPRISING A WATER-SOLUBLE SOAP AND AN ANTISEPTIC COMBINATION HAVING A SYNERGISTIC EFFECT CONSISTING OF FROM ABOUT 0.1% TO ABOUT 3.0% BY WEIGHT BASED UPON THE SOAP OF 2,2''-DIHYDROXY-3,5,6,3'',5'',6''-HEXACHLORODIPHENYL METHANE AND FROM ABOUT 3.0% TO ABOUT 0.1% BY WEIGHT BASED UPON THE SOAP OF 2,2''-DIHYDROXY-,3''-DIMETHYL-5,5''-DICHLORODIPHENY SULFIDE. 